scholarly journals Luminescent gold–thallium derivatives with a pyridine-containing 12-membered aza-thioether macrocycle

2021 ◽  
Author(s):  
Francesco Caddeo ◽  
Vanesa Fernández-Moreira ◽  
Massimiliano Arca ◽  
Anna Pintus ◽  
Antonio Laguna ◽  
...  
Keyword(s):  
Structural Motif

The heterometallic TlI/AuI complex {[Au(C6F5)2Tl]2(L)}n has an unprecedented polymeric structural motif with a metallic pseudo-rhombic Au2Tl2 core that repeats itself to form zig-zag polymers and shows a thermochromic behaviour.

A Chemical Perspective to the Anti-Amyloid Action of Compounds and a Nanoparticle Based Assay for Screening Amyloid Inhibitors

2020 ◽  
Author(s):  
Nidhi Gour ◽  
Bharti Koshti
Keyword(s):  
Memory Loss ◽  
Cost Effective ◽  
Structural Motif ◽  
Rapid Screening ◽  
Stacking Interactions ◽  
Aromatic Rings ◽  
Amyloid Fibers ◽  
Aromatic Stacking ◽  
Cost Effective Technique ◽  
The Brain

Aggregation of amyloid beeta 1-42 (Aβ<sub>42</sub>) peptide causes the formation of clustered deposits knows as amyloid plaques in the brain which leads to neuronal dysfunction and memory loss and associated with many neurological disorders including Alzheimer’s and Parkinson’s. Aβ<sub>42</sub> has core structural motif with phenylalanine at the 19 and 20 positions. The diphenylalanine (FF) residue plays a crucial role in the formation of amyloid fibers and serves as model peptide for studying Aβ<sub>42 </sub>aggregation. FF self-assembles to well-ordered tubular morphology via aromatic pi-pi stackings. Our studies, suggest that the aromatic rings present in the anti-amyloidogenic compounds may interact with the pi-pi stacking interactions present in the FF. Even the compounds which do not have aromatic rings, like cyclodextrin and cucurbituril show anti-amyloid property due to the binding of aromatic ring inside the guest cavity. Hence, our studies also suggest that compounds which may have a functional moiety capable of interacting with the aromatic stacking interactions might be tested for their anti-amyloidogenic properties. Further, in this manuscript, we have proposed two novel nanoparticle based assays for the rapid screening of amyloid inhibitors. In the first assay, interaction between biotin-tagged FF peptide and the streptavidin labelled gold nanoparticles (s-AuNPs) were used. In another assay, thiol-Au interactions were used to develop an assay for detection of amyloid inhibitors. It is envisaged that the proposed analytical method will provide a simple, facile and cost effective technique for the screening of amyloid inhibitors and may be of immense practical implications to find the therapeutic remedies for the diseases associated with the protein aggregation.

Combiphore (Structure and Ligand Based Pharmacophore) - Approach for the Design of GPR40 Modulators in the Management of Diabetes

2020 ◽  
Vol 17 (2) ◽  
pp. 233-247
Author(s):  
Krishna A. Gajjar ◽  
Anuradha K. Gajjar
Keyword(s):  
Molecular Docking ◽  
Structural Information ◽  
Docking Studies ◽  
Structural Motif ◽  
Roc Curve Analysis ◽  
Ligand Complex ◽  
Discovery Studio ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Pharmacophore Models

Background: Pharmacophore mapping and molecular docking can be synergistically integrated to improve the drug design and discovery process. A rational strategy, combiphore approach, derived from the combined study of Structure and Ligand based pharmacophore has been described to identify novel GPR40 modulators. Methods: DISCOtech module from Discovery studio was used for the generation of the Structure and Ligand based pharmacophore models which gave hydrophobic aromatic, ring aromatic and negative ionizable as essential pharmacophoric features. The generated models were validated by screening active and inactive datasets, GH scoring and ROC curve analysis. The best model was exposed as a 3D query to screen the hits from databases like GLASS (GPCR-Ligand Association), GPCR SARfari and Mini-Maybridge. Various filters were applied to retrieve the hit molecules having good drug-like properties. A known protein structure of hGPR40 (pdb: 4PHU) having TAK-875 as ligand complex was used to perform the molecular docking studies; using SYBYL-X 1.2 software. Results and Conclusion: Clustering both the models gave RMSD of 0.89. Therefore, the present approach explored the maximum features by combining both ligand and structure based pharmacophore models. A common structural motif as identified in combiphore for GPR40 modulation consists of the para-substituted phenyl propionic acid scaffold. Therefore, the combiphore approach, whereby maximum structural information (from both ligand and biological protein) is explored, gives maximum insights into the plausible protein-ligand interactions and provides potential lead candidates as exemplified in this study.

scholarly journals Roles of the 14-3-3 gene family in cotton flowering

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Na Sang ◽  
Hui Liu ◽  
Bin Ma ◽  
Xianzhong Huang ◽  
Lu Zhuo ◽  
...  
Keyword(s):  
Gene Family ◽  
Protein Interactions ◽  
Leucine Zipper ◽  
Expression Patterns ◽  
Bimolecular Fluorescence Complementation ◽  
Structural Motif ◽  
Virus Induced Gene Silencing ◽  
Protein Protein Interactions ◽  
Basic Leucine Zipper ◽  
Genome Wide

Abstract Background In plants, 14-3-3 proteins, also called GENERAL REGULATORY FACTORs (GRFs), encoded by a large multigene family, are involved in protein–protein interactions and play crucial roles in various physiological processes. No genome-wide analysis of the GRF gene family has been performed in cotton, and their functions in flowering are largely unknown. Results In this study, 17, 17, 31, and 17 GRF genes were identified in Gossypium herbaceum, G. arboreum, G. hirsutum, and G. raimondii, respectively, by genome-wide analyses and were designated as GheGRFs, GaGRFs, GhGRFs, and GrGRFs, respectively. A phylogenetic analysis revealed that these proteins were divided into ε and non-ε groups. Gene structural, motif composition, synteny, and duplicated gene analyses of the identified GRF genes provided insights into the evolution of this family in cotton. GhGRF genes exhibited diverse expression patterns in different tissues. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that the GhGRFs interacted with the cotton FLOWERING LOCUS T homologue GhFT in the cytoplasm and nucleus, while they interacted with the basic leucine zipper transcription factor GhFD only in the nucleus. Virus-induced gene silencing in G. hirsutum and transgenic studies in Arabidopsis demonstrated that GhGRF3/6/9/15 repressed flowering and that GhGRF14 promoted flowering. Conclusions Here, 82 GRF genes were identified in cotton, and their gene and protein features, classification, evolution, and expression patterns were comprehensively and systematically investigated. The GhGRF3/6/9/15 interacted with GhFT and GhFD to form florigen activation complexs that inhibited flowering. However, GhGRF14 interacted with GhFT and GhFD to form florigen activation complex that promoted flowering. The results provide a foundation for further studies on the regulatory mechanisms of flowering.

scholarly journals Mimicking of the histidine brace structural motif in molecular copper(I) compounds

2021 ◽  
Author(s):  
Raphael Peifer ◽  
Lars Müller ◽  
Santina Hoof ◽  
Fabian Beckmann ◽  
Beatrice Cula ◽  
...  
Keyword(s):  
Structural Motif

scholarly journals Bio-Guided Isolation of Antimalarial Metabolites from the Coculture of Two Red Sea Sponge-Derived Actinokineospora and Rhodococcus spp.

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 109
Author(s):  
Hani A. Alhadrami ◽  
Bathini Thissera ◽  
Marwa H. A. Hassan ◽  
Fathy A. Behery ◽  
Che Julius Ngwa ◽  
...  
Keyword(s):  
Red Sea ◽  
Antimalarial Activity ◽  
Axenic Culture ◽  
Trna Synthetase ◽  
Structural Motif ◽  
Natural Habitats ◽  
Signalling Molecules ◽  
Chemical Signalling ◽  
Axenic Conditions

Coculture is a productive technique to trigger microbes’ biosynthetic capacity by mimicking the natural habitats’ features principally by competition for food and space and interspecies cross-talks. Mixed cultivation of two Red Sea-derived actinobacteria, Actinokineospora spheciospongiae strain EG49 and Rhodococcus sp. UR59, resulted in the induction of several non-traced metabolites in their axenic cultures, which were detected using LC–HRMS metabolomics analysis. Antimalarial guided isolation of the cocultured fermentation led to the isolation of the angucyclines actinosporins E (1), H (2), G (3), tetragulol (5) and the anthraquinone capillasterquinone B (6), which were not reported under axenic conditions. Interestingly, actinosporins were previously induced when the axenic culture of the Actinokineospora spheciospongiae strain EG49 was treated with signalling molecule N-acetyl-d-glucosamine (GluNAc); this finding confirmed the effectiveness of coculture in the discovery of microbial metabolites yet to be discovered in the axenic fermentation with the potential that could be comparable to adding chemical signalling molecules in the fermentation flask. The isolated angucycline and anthraquinone compounds exhibited in vitro antimalarial activity and good biding affinity against lysyl-tRNA synthetase (PfKRS1), highlighting their potential developability as new antimalarial structural motif.

scholarly journals PPO-Inhibiting Herbicides and Structurally Relevant Schiff Bases: Evaluation of Inhibitory Activities against Human Protoporphyrinogen Oxidase

Processes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 383
Author(s):  
Milan Jakubek ◽  
Michal Masařík ◽  
Tomáš Bříza ◽  
Robert Kaplánek ◽  
Kateřina Veselá ◽  
...  
Keyword(s):  
Melting Temperature ◽  
Schiff Bases ◽  
Anticancer Agents ◽  
Protoporphyrin Ix ◽  
Docking Study ◽  
Structural Motif ◽  
Protoporphyrinogen Oxidase ◽  
Ic50 Values ◽  
Inhibitory Activities ◽  
Potential Inhibitors

The study of human protoporphyrinogen oxidase (hPPO) inhibition can contribute significantly to a better understanding of some pathogeneses (e.g., porphyria, herbicide exposure) and the development of anticancer agents. Therefore, we prepared new potential inhibitors with Schiff base structural motifs (2-hydroxybenzaldehyde-based Schiff bases 9–13 and chromanone derivatives 17–19) as structurally relevant to PPO herbicides. The inhibitory activities (represented by the half maximal inhibitory concentration (IC50) values) and enzymatic interactions (represented by the hPPO melting temperatures) of these synthetic compounds and commercial PPO herbicides used against hPPO were studied by a protoporphyrin IX fluorescence assay. In the case of PPO herbicides, significant hPPO inhibition and changes in melting temperature were observed for oxyfluorten, oxadiazon, lactofen, butafenacil, saflufenacil, oxadiargyl, chlornitrofen, and especially fomesafen. Nevertheless, the prepared compounds did not display significant inhibitory activity or changes in the hPPO melting temperature. However, a designed model of hPPO inhibitors based on the determined IC50 values and a docking study (by using AutoDock) found important parts of the herbicide structural motif for hPPO inhibition. This model could be used to better predict PPO herbicidal toxicity and improve the design of synthetic inhibitors.

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